Anti-PD-1 antibody decreases tumour-infiltrating regulatory T cells

被引:84
|
作者
Yoshida, Kazushige [1 ]
Okamoto, Masanori [1 ]
Sasaki, Jun [1 ]
Kuroda, Chika [2 ]
Ishida, Haruka [2 ]
Ueda, Katsuya [2 ]
Ideta, Hirokazu [1 ]
Kamanaka, Takayuki [1 ]
Sobajima, Atsushi [1 ]
Takizawa, Takashi [1 ]
Tanaka, Manabu [3 ]
Aoki, Kaoru [4 ]
Uemura, Takeshi [2 ]
Kato, Hiroyuki [1 ]
Haniu, Hisao [2 ]
Saito, Naoto [2 ]
机构
[1] Shinshu Univ, Dept Orthopaed Surg, Sch Med, Matsumoto, Nagano, Japan
[2] Shinshu Univ, Inst Biomed Sci, Interdisciplinary Cluster Cutting Edge Res, Asahi 3-1-1, Matsumoto, Nagano 3908621, Japan
[3] Okaya City Hosp, Dept Orthoped Surg, Okaya, Japan
[4] Shinshu Univ, Sch Hlth Sci, Phys Therapy Div, Sch Med, Matsumoto, Nagano, Japan
关键词
PD-1; Treg; Osteosarcoma; Anti-PD-1; antibody; IFN-GAMMA; CANCER; PD-L1; BLOCKADE; EXPRESSION; SUPPRESSION; EFFICACY; THERAPY; ROLES; FOXP3;
D O I
10.1186/s12885-019-6499-y
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Background There are many types of therapies for cancer. In these days, immunotherapies, especially immune checkpoint inhibitors, are focused on. Though many types of immune checkpoint inhibitors are there, the difference of effect and its mechanism are unclear. Some reports suggest the response rate of anti-PD-1 antibody is superior to that of anti-PD-L1 antibody and could potentially produce different mechanisms of action. On the other hand, Treg also express PD-1; however, their relationship remains unclear. Methods In this study, we used osteosarcoma cell lines in vitro and osteosarcoma mouse model in vivo. In vitro, we analyzed the effect of IFN gamma for expression of PD-L1 on the surface of cell lines by flowcytometry. In vivo, murine osteosarcoma cell line LM8 was subcutaneously transplanted into the dorsum of mice. Mouse anti-PD-1 antibody was intraperitoneally administered. we analysed the effect for survival of anti-PD-1 antibody and proportion of T cells in the tumour by flowcytometry. Results We discovered that IFN gamma increased PD-L1 expression on the surface of osteosarcoma cell lines. In assessing the relationship between anti-PD-1 antibody and Treg, we discovered the administration of anti-PD-1 antibody suppresses increases in tumour volume and prolongs overall survival time. In the tumour microenvironment, we found that the administration of anti-PD-1 antibody decreased Treg within the tumour and increased tumour-infiltrating lymphocytes. Conclusions Here we clarify for the first time an additional mechanism of anti-tumour effect-as exerted by anti-PD-1 antibody decreasing Treg- we anticipate that our findings will lead to the development of new methods for cancer treatment.
引用
收藏
页数:10
相关论文
共 50 条
  • [21] Intratumoral follicular regulatory T cells curtail anti-PD-1 treatment efficacy
    Eschweiler, Simon
    Clarke, James
    Ramirez-Suastegui, Ciro
    Panwar, Bharat
    Madrigal, Ariel
    Chee, Serena J.
    Karydis, Ioannis
    Woo, Edwin
    Alzetani, Aiman
    Elsheikh, Somaia
    Hanley, C. J.
    Thomas, G. J.
    Friedmann, Peter S.
    Sanchez-Elsner, Tilman
    Ay, Ferhat
    Ottensmeier, Christian H.
    Vijayanand, Pandurangan
    NATURE IMMUNOLOGY, 2021, 22 (08) : 1052 - +
  • [22] Prognostic impact of tumour-infiltrating Th2 and regulatory T cells in classical Hodgkin lymphoma
    Schreck, Sabine
    Friebel, Daniela
    Buettner, Maike
    Distel, Luitpold
    Grabenbauer, Gerhard
    Young, Lawrence S.
    Niedobitek, Gerald
    HEMATOLOGICAL ONCOLOGY, 2009, 27 (01) : 31 - 39
  • [23] Combination of Anti-PD-1 Antibody, Anlotinib and Pegaspargase "Sandwich" With Radiotherapy in Localized Natural Killer/T Cell Lymphoma
    Sun, Peng
    Wang, Yu
    Yang, Hang
    Chen, Cui
    Nie, Man
    Sun, Xiao-Qing
    He, Xiao-Hua
    Huang, Kang-Ming
    Huang, Jia-Jia
    Li, Zhi-Ming
    FRONTIERS IN IMMUNOLOGY, 2022, 13
  • [24] Interaction between tumour-infiltrating B cells and T cells controls the progression of hepatocellular carcinoma
    Garnelo, Marta
    Tan, Alex
    Her, Zhisheng
    Yeong, Joe
    Lim, Chun Jye
    Chen, Jinmiao
    Lim, Kiat Hon
    Weber, Achim
    Chow, Pierce
    Chung, Alexander
    Ooi, London Lucien P. J.
    Toh, Han Chong
    Heikenwalder, Mathias
    Ng, Irene O. L.
    Nardin, Alessandra
    Chen, Qingfeng
    Abastado, Jean-Pierre
    Chew, Valerie
    GUT, 2017, 66 (02) : 342 - 351
  • [25] Combination Foretinib and Anti-PD-1 Antibody Immunotherapy for Colorectal Carcinoma
    Fu, Yuyin
    Peng, Yujia
    Zhao, Shengyan
    Mou, Jun
    Zeng, Lishi
    Jiang, Xiaohua
    Yang, Chengli
    Huang, Cheng
    Li, Yuyan
    Lu, Yin
    Wu, Mengdan
    Yang, Yanfang
    Kong, Ting
    Lai, Qinhuai
    Wu, Yangping
    Yao, Yuqin
    Wang, Yuxi
    Gou, Lantu
    Yang, Jinliang
    FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY, 2021, 9
  • [26] Anti-PD-1 monoclonal antibody Cancer immunotherapy
    da Silva, R. Moreira
    DRUGS OF THE FUTURE, 2014, 39 (01) : 15 - 24
  • [27] Tissue biomarkers of response to anti-PD-1 immunotherapies in melanoma
    Adam, Julien
    Tomasic, Gorana
    Robert, Caroline
    ANNALES DE PATHOLOGIE, 2017, 37 (01) : 55 - 60
  • [28] Prognostic importance of tumour-infiltrating memory T cells in oesophageal squamous cell carcinoma
    Enomoto, K.
    Sho, M.
    Wakatsuki, K.
    Takayama, T.
    Matsumoto, S.
    Nakamura, S.
    Akahori, T.
    Tanaka, T.
    Migita, K.
    Ito, M.
    Nakajima, Y.
    CLINICAL AND EXPERIMENTAL IMMUNOLOGY, 2012, 168 (02) : 186 - 191
  • [29] The IFN-γ/PD-L1 axis between T cells and tumor microenvironment: hints for glioma anti-PD-1/PD-L1 therapy
    Qian, Jiawen
    Wang, Chen
    Wang, Bo
    Yang, Jiao
    Wang, Yuedi
    Luo, Feifei
    Xu, Junying
    Zhao, Chujun
    Liu, Ronghua
    Chu, Yiwei
    JOURNAL OF NEUROINFLAMMATION, 2018, 15
  • [30] Burgeoning Exploration of the Role of Natural Killer Cells in Anti-PD-1/PD-L1 Therapy
    Bai, Rilan
    Cui, Jiuwei
    FRONTIERS IN IMMUNOLOGY, 2022, 13